Abstract |
Metastatic death from uveal melanoma occurs almost exclusively with tumors showing monosomy of chromosome 3. However, approximately 5% of patients with a disomy 3 uveal melanoma develop metastases, and a further 5% of monosomy 3 uveal melanoma patients exhibit disease-free survival for >5 years. In the present study, whole-genome microarrays were used to interrogate four clinically well-defined subgroups of uveal melanoma: i) disomy 3 uveal melanoma with long-term survival; ii) metastasizing monosomy 3 uveal melanoma; iii) metastasizing disomy 3 uveal melanoma; and iv) monosomy 3 uveal melanoma with long-term survival. Cox regression and Kaplan-Meier survival analysis identified that amplification of the CNKSR3 gene (log-rank, P = 0.022) with an associated increase in its protein expression (log-rank, P = 0.011) correlated with longer patient survival. Although little is known about CNKSR3, the correlation of protein expression with increased survival suggests a biological function in uveal melanoma, possibly working to limit metastatic progression of monosomy 3 uveal melanoma cells.
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Authors | Sarah L Lake, Bertil E Damato, Helen Kalirai, Andrew R Dodson, Azzam F G Taktak, Bryony H Lloyd, Sarah E Coupland |
Journal | The American journal of pathology
(Am J Pathol)
Vol. 182
Issue 3
Pg. 678-87
(Mar 2013)
ISSN: 1525-2191 [Electronic] United States |
PMID | 23357503
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- CNKSR3 protein, human
- Enkephalins
- Membrane Proteins
- Neoplasm Proteins
- Protein Precursors
- proenkephalin
- RIPK1 protein, human
- Receptor-Interacting Protein Serine-Threonine Kinases
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Topics |
- Aged
- DNA Copy Number Variations
(genetics)
- Enkephalins
(metabolism)
- Female
- Gene Amplification
- Genes, Neoplasm
(genetics)
- Humans
- Immunohistochemistry
- Kaplan-Meier Estimate
- Male
- Melanoma
(genetics, pathology)
- Membrane Proteins
(genetics)
- Middle Aged
- Neoplasm Metastasis
- Neoplasm Proteins
(genetics, metabolism)
- Oligonucleotide Array Sequence Analysis
- Polymorphism, Single Nucleotide
(genetics)
- Protein Precursors
(metabolism)
- Receptor-Interacting Protein Serine-Threonine Kinases
(metabolism)
- Time Factors
- Uveal Neoplasms
(genetics, pathology)
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